A reduction in mechanical load-induced myofiber wounding and a consequent decrease in wound-mediated release of fibroblast growth factor (FGF) may contribute to muscle atrophy during spaceflight. To test this hypothesis we have utilized a terrestrial model of spaceflight (i.e. 14 days of head-down bedrest) to investigate the amount of myofiber wounding and FGF release which occurs during unloading. Myofiber wounding was assessed by determining the amount of the creatine kinase MM iosform present in the serum before and after bedrest. Serum acidic FGF (aFGF) and basic FGF (bFGF) levels were also determined pre and post bedrest. Needle biopsy was performed on the m. vastus lateralis of each subject pre and post bedrest. Muscle samples were cyrosectioned and myofiber cross-sectional area was determined using image analysis. A second group of subjects were treated similarly except that a resistive exercise program was used during bedrest to assess its value as an atrophy countermeasure. Bedrest alone caused significant (p<0.05;n-8) reductions in serum levels of both CKMM and aFGF. These decreases were paralleled by a significant (p<0.05) decrease in myofiber size. In contrast, bedrest plus resistive exercise resulted in significant (p<0,05;n=8) increases in serum levels of both CKMM and aFGF. These increases were paralleled by a significant (p<0.05;n=8) increase in the amount of myofiber-associated aFGF whereas myofiber size remained unchanged. These results suggest that mechanically induced, myofiber wound-mediated aFGF release plays an important role in the etiology of skeletal muscle atrophy due to mechanical unloading.